Polymeric complexes — LXI. Supramolecular structure, thermal properties, SS-DNA binding activity and antimicrobial activities of polymeric complexes of rhodanine hydrazone compounds

Journal of Molecular Liquids 215 (2016) 711–739

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Journal of Molecular Liquids journal homepage: www.elsevier.com/locate/molliq

Polymeric complexes — LXI. Supramolecular structure, thermal properties, SS-DNA binding activity and antimicrobial activities of polymeric complexes of rhodanine hydrazone compounds A.Z. El-Sonbati a, M.A. Diab a, A.A. El-Bindary a,⁎, M.M. Ghoneim b, M.T. Mohesien c, M.K. Abd El-Kader a a b c

Chemistry Department, Faculty of Science, Damietta University, Damietta 34517, Egypt Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt Botany Department, Faculty of Science, Damietta University, Damietta 34517, Egypt

a r t i c l e

i n f o

Article history: Received 21 October 2015 Received in revised form 8 November 2015 Accepted 2 December 2015 Available online xxxx Keywords: Co(II) complexes SS-DNA binding Molecular structure Antimicrobial activities

a b s t r a c t A series of new ligands 5-(4′-alkylphenylazo)-3-phenylamino-2-thioxothiazolidin-4-one (HLn) were synthesized from the coupling of 3-phenylamino-2-thioxothiazolidin-4-one with aniline and its p-derivatives. These ligands and their Co(II) polymeric complexes of the [(Co)2(Ln)2(HLn)(CH3COO)2(H2O)2]n have been deduced from elemental analyses, IR, 1H-NMR, X-ray diffraction and mass spectra as well as magnetic and thermal measurements. IR and 1H NMR studies reveal that the ligands (HLn) exist in the tautomeric enol/hydrazo form in both states with intramolecular hydrogen bonding. The important infrared (IR) spectral bands imply that HLn is coordinated to the metal ion in a monobasic tetradentate via NH (hydrazone), oxygen of the carbonyl group (CO), nitrogen of the NH (3-phenylamine) and thion sulfur (CS) group. The complexes are polymeric, non-electrolytes, paramagnetic and octahedral six-coordinated. The molecular and electronic structures of the investigated compounds (HLn) were also studied using quantum chemical calculations. The salmon sperm DNA (SS-DNA) binding activity of the ligands (HLn) was studied by absorption spectra. The interaction between ligands (HLn) and SS-DNA shows hypochromism effect coupled with obvious bathochromism. The values of binding constant are correlated with Hammett's constant (σR). The cytotoxic activity of ligands (HLn) and their Co(II) complexes were tested against two human cancer HePG-2 (Hepatocellular carcinoma) and MCF-7 (breast cancer). The antioxidant activities of ligands (HLn) and their Co(II) complexes were performed by ABTS method. The antimicrobial activity of ligands HLn and their Co(II) complexes were tested against Gram negative bacteria (Escherichia coli), Gram positive bacteria (Staphylococcus aureus) and yeast (Candida albicans). © 2015 Elsevier B.V. All rights reserved.

1. Introduction In recent past, a variety of molecules based on rhodanine have been synthesized and evaluated with improved pharmacological activities due to their wide range of pharmacological and clinical utilization [1–8]. Rhodanine compounds and their complexes play an important role in biological reactions [9,10]. These molecules are considered as good antimycobacterial, antifungal, antidiabetic, antihepatitis C virus (HCV), anticancer, antioxidant, pesticidal, antihypertensive and antineoplastic agents. These molecules attracted much attention and encouraged the chemists and biologists to extensive investigations or molecular manipulations [5,11]. Chemical properties of rhodanine and its derivatives are of interest due to coordination capacity and their use as metal extracting agents; these molecules are capable of having

⁎ Corresponding author. E-mail address: [email protected] (A.A. El-Bindary).

http://dx.doi.org/10.1016/j.molliq.2015.12.010 0167-7322/© 2015 Elsevier B.V. All rights reserved.

keto–enol tautomers. Hydrazone compounds of rhodanine usually react as chelating with transition metal ions by bonding through the oxygen and hydrazinic nitrogen atoms [1,8], as they form a stable sixmembered characterization of 5-(4′-alkylphenylazo)-3-phenylamino2-thioxothiazolidin-4-one (HLn) and their polymer complexes with cobalt(II). HLn act as monobasic tetradentate reacting with Co(II) through the CO (rhodanine moiety), hydrazinic N with displacement of hydrogen atom, CS (rhodanine moiety) and amidic N. DNA is one of the most important biomacromolecules in life processes because it carries inheritance information and instructs the biological synthesis of proteins and enzyme through the process of replication and transcription of genetic information. DNA plays an important role in the process of storing, copying and transmitting gene messages. DNA is also a major target for drugs and some harmful chemicals, and the studies on the binding nature of these small molecules to DNA are important and fundamental issues on life science because these drugs and chemicals can significantly influence the genetic information expression and result in some diseases

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Fig. 1. Structure of ligands (HLn).

Table 1 Physical properties and elemental analyses data of the ligands (HLn) and their Co(II) complexes (1–5). % Exp. (calc.) Compound HL1 (1) HL2 (2) HL3 (3) HL4 (4) HL5 (5) a

M.P. (°C) 131 – 161 – 164 – 164 – 178 –

Composition C

H

N

M

53.60 (53.63) 46.22 (46.43) 56.00 (56.14) 48.03 (48.15) 54.90 (54.88) 46.77 (46.89) 49.70 (49.66) 43.14 (43.32) 48.30 (48.26) 42.12 (42.34)

4.00 (3.91) 3.56 (3.72) 4.10 (4.09) 3.66 (3.86) 3.70 (3.66) 3.35 (3.51) 3.10 (3.03) 2.89 (3.02) 3.00 (2.95) 2.87 (2.95)

15.60 (15.64) 12.12 (12.50) 16.40 (16.37) 12.74 (12.96) 17.10 (17.07) 12.04 (13.40) 15.50 (15.45) 12.03 (12.38) 18.80 (18.77) 14.86 (15.12)

– 8.37 (8.77) – 8.78 (9.10) –

(9.40) – 8.47 (8.68) – 8.15 (8.49)

Microanalytical data as well as metal estimations are in good agreement with the stoichiometry of the proposed complexes. The excellent agreement between calculated and experimental data supports the assignment suggested in the present work. c HL1–HL5 are the ligands and L1–L5 are the anions. b

[(Co)2(HL1)(L1)2(CH3COO)2(H2O)2]n

[(Co)2(HL2)(L2)2(CH3COO)2(H2O)2]n

[(Co)2(HL3)(L3)2(CH3COO)2(H2O)2]n

[(Co)2(HL4)(L4)2(CH3COO)2(H2O)2]n

[(Co)2(HL5)(L5)2(CH3COO)2(H2O)2]n

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

Fig. 2. Proposed structure of Co(II) complexes.

related to the cell proliferation and differentiation [12,13]. In our laboratories, we have initiated a series of studies of the effects of substituents at p-position of the aromatic amine on the stoichiometries of

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the complexes of these ligands with cobalt acetate [7]. The Co(II) complexes attracted attention in coordination chemistry, thermal stability and biological function of some bimetallic complexes for which structural information was obtained by spectrochemical and magnetochemical means; due to the Co(II) in d7 is known, in four coordinate as tetrahedral and six coordinate as octahedral stereochemistries [14–18]. The aim of this work is to, synthesis and characterize of Co(II) complexes of 5-(4′-alkylphenylazo)-3-phenylamino-2-thioxothiazolidin-4one (HLn) by elemental analyses, IR, 1H & 13C NMR, UV–Vis, X-ray diffractometer, magnetic moment, molar conductance, and thermal analysis. Molecular and electronic structures of the ligands (HLn) have been discussed. Mass spectra and X-ray diffraction analysis of ligands (HL1, HL3 and HL4) were discussed. The activation thermodynamic parameters, such as activation energy (Ea), enthalpy (ΔH⁎), entropy (ΔS⁎), and Gibbs free energy change of the decomposition (ΔG⁎) were calculated using Coats–Redfern and Horowitz–Metzger methods. The

Fig. 3. The molecular structures for HLn.

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Table 2 The selected geometric parameters for HL1. Bond lengths (Å) C(25)–H(38) C(25)–H(37) C(25)–H(36) C(21)–H(35) C(20)–H(34) C(18)–H(33) C(17)–H(32) C(11)–H(31) C(10)–H(30) C(9)–H(29) C(8)–H(28) C(7)–H(27) N(6)–H(26) C(17)–C(22) C(21)–C(22) C(20)–C(21) C(19)–C(20) C(18)–C(19) C(17)–C(18) C(7)–C(12) C(11)–C(12) C(10)–C(11) C(9)–C(10) C(8)–C(9) C(7)–C(8) H(23)–O(13) N(16)–H(23) C(22)–N(16) N(15)–N(16) C(12)–N(6) N(2)–N(6) C(19)–O(24) C(5)–N(15) C(3)–S(14) C(1)–O(13) C(5)–C(1) S(4)–C(5) C(3)–S(4) N(2)–C(3) C(1)–N(2) O(24)–C(25)

Bond angles (°) 1.113 1.113 1.113 1.104 1.102 1.104 1.103 1.104 1.103 1.103 1.103 1.103 1.051 1.345 1.345 1.343 1.348 1.347 1.342 1.346 1.345 1.342 1.342 1.342 1.342 1.003 1.037 1.273 1.249 1.272 1.351 1.375 1.281 1.575 1.221 1.377 1.479 1.794 1.374 1.374 1.409

H(38)–C(25)–H(37) H(38)–C(25)–H(36) H(38)–C(25)–O(24) H(37)–C(25)–H(36) H(37)–C(25)–O(24) H(36)–C(25)–O(24) C(19)–O(24)–C(25) H(34)–C(20)–C(21) H(34)–C(20)–C(19) C(21)–C(20)–C(19) C(20)–C(19)–C(18) C(20)–C(19)–O(24) C(18)–C(19)–O(24) H(33)–C(18)–C(19) H(33)–C(18)–C(17) C(19)–C(18)–C(17) H(35)–C(21)–C(22) H(35)–C(21)–C(20) C(22)–C(21)–C(20) H(32)–C(17)–C(22) H(32)–C(17)–C(18) C(22)–C(17)–C(18) C(17)–C(22)–C(21) C(17)–C(22)–N(16) C(21)–C(22)–N(16) H(23)–N(16)–C(22) H(23)–N(16)–N(15) C(22)–N(16)–N(15) C(5)–S(4)–C(3) N(16)–N(15)–C(5) H(30)–C(10)–C(11) H(30)–C(10)–C(9) C(11)–C(10)–C(9) H(29)–C(9)–C(10) H(29)–C(9)–C(8) C(10)–C(9)–C(8) H(28)–C(8)–C(9) H(28)–C(8)–C(7) C(9)–C(8)–C(7) H(31)–C(11)–C(12) H(31)–C(11)–C(10) C(12)–C(11)–C(10) H(27)–C(7)–C(12) H(27)–C(7)–C(8) C(12)–C(7)–C(8) C(7)–C(12)–C(11) C(7)–C(12)–N(6)

Bond angles (°) 111.887 108.169 110.347 108.167 110.354 107.776 118.767 116.943 120.926 122.131 115.683 125.543 118.775 118.575 118.627 122.798 120.437 118.181 121.382 121.128 118.067 120.805 117.202 122.386 120.412 122.189 108.605 129.206 96.437 116.122 120.035 119.886 120.079 120.144 120.146 119.709 119.865 120.019 120.116 120.723 118.691 120.586 121.023 118.446 120.531 118.978 122.597

C(11)–C(12)–N(6) H(26)–N(6)–C(12) H(26)–N(6)–N(2) C(12)–N(6)–)–N(2) S(14)–C(3)–S(4) S(14)–C(3)–N(2) S(4)–C(3)–N(2) O(13)–H(23)–N(16) N(6)–N(2)–C(3) N(6)–N(2)–C(1) C(3)–N(2)–C(1) H(23)–O(13)–C(1) N(15)–C(5)–C(1) N(15)–C(5)–S(4) C(1)–C(5)–S(4) O(13)–C(1)–C(5) O(13)–C(1)–N(2) C(5)–C(1)–N(2) Dihedral angle (°) C(18)–C(17)–C(22)–N(16) C(20)–C(21)–C(22)–N(16) C(8)–C(7)–C(12)–N(6) C(10)–C(11)–C(12)–N(6) C(7)–C(12)–N(6)–N(2) N(15)–C(5)–C(1)–N(2)

118.424 114.354 116.442 122.051 125.084 129.758 105.156 154.903 125.249 123.904 110.84 108.968 116.374 131.246 112.38 115.027 129.783 115.187 179.997 -179.99 179.986 -179.988 -32.896 -179.655

Table 3 The selected geometric parameters for HL2. Bond lengths (Å) C(23)–H(37) C(23)–H(36) C(23)–H(35) C(21)–H(34) C(20)–H(33) C(18)–H(32) C(17)–H(31) C(11)–H(30) C(10)–H(29) C(9)–H(28) C(8)–H(27) C(7)–H(26) N(6)–H(25) C(17)–C(22) C(21)–C(22) C(20)–C(21) C(19)–C(20) C(18)–C(19) C(17)–C(18) C(7)–C(12) C(11)–C(12)

Bond angles (°) 1.114 1.114 1.113 1.104 1.103 1.103 1.103 1.104 1.103 1.103 1.103 1.103 1.051 1.346 1.346 1.342 1.344 1.344 1.343 1.346 1.345

H(37)–C(23)–H(36) H(37)–C(23)–H(35) H(37)–C(23)–C(19) H(36)–C(23)–H(35) H(36)–C(23)–C(19) H(35)–C(23)–C(19) H(33)–C(20)–C(21) H(33)–C(20)–C(19) C(21)–C(20)–C(19) C(20)–C(19)–C(18) C(20)–C(19)–C(23) C(18)–C(19)–C(23) H(32)–C(18)–C(19) H(32)–C(18)–C(17) C(19)–C(18)–C(17) H(34)–C(21)–C(22) H(34)–C(21)–C(20) C(22)–C(21)–C(20) H(31)–C(17)–C(22) H(31)–C(17)–C(18) C(22)–C(17)–C(18)

Bond angles (°) 108.481 107.466 110.299 107.519 110.261 112.668 119.462 119.492 121.045 118.008 120.302 121.69 119.877 119.118 121.006 120.811 118.114 121.075 121.077 117.833 121.09

H(25)–N(6)–C(12) H(25)–N(6)–N(2) C(12)–N(6)–N(2) S(14)–C(3)–S(4) S(14)–C(3)–N(2) S(4)–C(3)–N(2) O(13)–H(24)–N(16) N(6)–N(2)–C(3) N(6)–N(2)–C(1) C(3)–N(2)–C(1) H(24)–O(13)–C(1) N(15)–C(5)–C(1) N(15)–C(5)–S(4) C(1)–C(5)–S(4) O(13)–C(1)–C(5) O(13)–C(1)–N(2) C(5)–C(1)–N(2) Dihedral angle (°) C(18)–C(17)–C(22)–N(16) C(20)–C(21)–C(22)–N(16) C(8)–C(7)–C(12)–N(6)

114.364 116.46 122.051 125.08 129.763 105.156 154.915 125.252 123.907 110.834 108.969 116.371 131.248 112.381 115.024 129.783 115.191 −179.998 −179.998 179.979

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Table 3 (continued) Bond lengths (Å) C(10)–C(11) C(9)–C(10) C(8)–C(9) C(7)–C(8) H(24)–O(13) N(16)–H(24) C(22)–N(16) N(15)–N(16) C(12)–N(6) N(2)–N(6) C(19)–C(23) C(5)–N(15) C(3)–S(14) C(1)–O(13) C(5)–C(1) S(4)–C(5) C(3)–S(4) N(2)–C(3) C(1)–N(2)

Bond angles (°) 1.342 1.342 1.342 1.342 1.004 1.037 1.274 1.249 1.272 1.351 1.51 1.281 1.575 1.221 1.377 1.479 1.794 1.374 1.374

C(17)–C(22)–C(21) C(17)–C(22)–N(16) C(21)–C(22)–N(16) H(24)–N(16)–C(22) H(24)–N(16)–N(15) C(22)–N(16)–N(15) C(5)–S(4)–C(3) N(16)–N(15)–C(5) H(29)–C(10)–C(11) H(29)–C(10)–C(9) C(11)–C(10)–C(9) H(28)–C(9)–C(10) H(28)–C(9)–C(8) C(10)–C(9)–C(8) H(27)–C(8)–C(9) H(27)–C(8)–C(7) C(9)–C(8)–C(7) H(30)–C(11)–C(12) H(30)–C(11)–C(10) C(12)–C(11)–C(10) H(26)–C(7)–C(12) H(26)–C(7)–C(8) C(12)–C(7)–C(8) C(7)–C(12)–C(11) C(7)–C(12)–N(6) C(11)–C(12)–N(6)

Bond angles (°) 117.775 122.127 120.097 122.19 108.581 129.228 96.438 116.139 120.036 119.883 120.081 120.147 120.145 119.708 119.867 120.016 120.117 120.723 118.695 120.581 121.026 118.444 120.53 118.981 122.586 118.431

C(10)–C(11)–C(12)–N(6) C(7)–C(12)–N(6)–N(2) N(15)–C(5)–C(1)–N(2)

−179.979 −32.812 −179.688

Table 4 The selected geometric parameters for HL3. Bond lengths (Å) C(21)–H(34) C(20)–H(33) C(19)–H(32) C(18)–H(31) C(17)–H(30) C(11)–H(29) C(10)–H(28) C(9)–H(27) C(8)–H(26) C(7)–H(25) N(6)–H(24) C(17)–C(22) C(21)–C(22) C(20)–C(21) C(19)–C(20) C(18)–C(19) C(17)–C(18) C(7)–C(12) C(11)–C(12) C(10)–C(11) C(9)–C(10) C(8)–C(9) C(7)–C(8) H(23)–O(13) N(16)–H(23) C(22)–N(16) N(15)–N(16) C(12)–N(6) N(2)–N(6) C(5)–N(15) C(3)–S(14) C(1)–O(13) C(5)–C(1) S(4)–C(5) C(3)–S(4) N(2)–C(3) C(1)–N(2)

Bond angles (°) 1.104 1.103 1.103 1.103 1.103 1.104 1.103 1.103 1.103 1.103 1.051 1.347 1.347 1.342 1.341 1.341 1.343 1.346 1.345 1.342 1.342 1.342 1.342 1.003 1.037 1.274 1.249 1.272 1.351 1.281 1.575 1.221 1.377 1.479 1.794 1.374 1.374

H(33)–C(20)–C(21) H(33)–C(20)–C(19) C(21)–C(20)–C(19) H(32)–C(19)–C(20) H(32)–C(19)–C(18) C(20)–C(19)–C(18) H(31)–C(18)–C(19) H(31)–C(18)–C(17) C(19)–C(18)–C(17) H(34)–C(21)–C(22) H(34)–C(21)–C(20) C(22)–C(21)–C(20) H(30)–C(17)–C(22) H(30)–C(17)–C(18) C(22)–C(17)–C(18) C(17)–C(22)–C(21) C(17)–C(22)–N(16) C(21)–C(22)–N(16) H(23)–N(16)–C(22) H(23)–N(16)–N(15) C(22)–N(16)–N(15) C(5)–S(4)–C(3) N(16)–N(15)–C(5) H(28)–C(10)–C(11) H(28)–C(10)–C(9) C(11)–C(10)–C(9) H(27)–C(9)–C(10) H(27)–C(9)–C(8) C(10)–C(9)–C(8) H(26)–C(8)–C(9) H(26)–C(8)–C(7) C(9)–C(8)–C(7) H(29)–C(11)–C(12) H(29)–C(11)–C(10) C(12)–C(11)–C(10) H(25)–C(7)–C(12) H(25)–C(7)–C(8) C(12)–C(7)–C(8) C(7)–C(12)–C(11) C(7)–C(12)–N(6) C(11)–C(12)–N(6)

Bond angles (°) 120.073 119.833 120.094 120.261 120.264 119.475 119.779 120.051 120.17 120.84 118.03 121.13 121.177 117.779 121.044 118.088 121.969 119.943 122.183 108.56 129.257 96.436 116.153 120.033 119.886 120.081 120.146 120.15 119.704 119.864 120.017 120.119 120.724 118.692 120.584 121.023 118.448 120.529 118.98 122.597 118.422

O(13)–H(23)–N(16) N(6)–N(2)–C(3) N(6)–N(2)–C(1) C(3)–N(2)–C(1) H(23)–O(13)–C(1) N(15)–C(5)–C(1) N(15)–C(5)–S(4) C(1)–C(5)–S(4) O(13)–C(1)–C(5) O(13)–C(1)–N(2) C(5)–C(1)–N(2) Dihedral angle (°) C(18)–C(17)–C(22)–N(16) C(20)–C(21)–C(22)–N(16) C(8)–C(7)–C(12)–N(6) C(10)–C(11)–C(12)–N(6) C(7)–C(12)–N(6)–N(2) N(15)–C(5)–C(1)–N(2)

154.932 125.247 123.915 110.831 108.97 116.365 131.255 112.381 115.021 129.784 115.192 179.985 −179.985 179.987 −179.978 −32.818 −179.634

(continued on next page)

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Table 4 (continued) Bond lengths (Å)

Bond angles (°) H(24)–N(6)–C(12) H(24)–N(6)–N(2) C(12)–N(6)–N(2) S(14)–C(3)–S(4) S(14)–C(3)–N(2) S(4)–C(3)–N(2)

salmon sperm DNA binding activity of the ligands (HLn) was studied by absorption spectra measurements.

Bond angles (°) 114.354 116.459 122.069 125.08 129.76 105.159

sperm DNA (SS-DNA) was purchased from SRL (India). Double distilled water was used to prepare all buffer solutions. 2.2. Preparation of azodye ligands

2. Experimental 2.1. Materials 3-Phenylamino-2-thioxtiazolidin-4-one was prepared previously [1,8,13]. The standard chemical cobalt acetate, aniline and 4alkylanilines (alkyl: CH3, OCH3, Cl and NO2) were purchased from Sigma and Aldrich and used without any further purification. Salmon

Preparation of 5-(4′-alkylphenylazo)-3-phenylamino-2thioxothiazolidin-4-one (HLn) (Fig. 1); 25 ml of distilled water containing hydrochloric acid was added to aniline or a 4-alkyl-aniline. To the resulting mixture stirred and cooled to 0 °C, a solution of sodium nitrite 0.01 mol in 20 ml of water was added dropwise. The formed diazonium chloride was consecutively coupled with an alkaline solution of 3phenylamino-2-thioxothiazolidin-4-one 0.01 mol in 10 ml of pyridine.

Table 5 The selected geometric parameters for HL4. Bond lengths (Å) C(21)–H(34) C(20)–H(33) C(18)–H(32) C(17)–H(31) C(11)–H(30) C(10)–H(29) C(9)–H(28) C(8)–H(27) C(7)–H(26) N(6)–H(25) C(17)–C(22) C(21)–C(22) C(20)–C(21) C(19)–C(20) C(18)–C(19) C(17)–C(18) C(7)–C(12) C(11)–C(12) C(10)–C(11) C(9)–C(10) C(8)–C(9) C(7)–C(8) H(24)–O(13) N(16)–H(24) C(22)–N(16) N(15)–N(16) C(12)–N(6) N(2)–N(6) C(19)–Cl(23) C(5)–N(15) C(3)–S(14) C(1)–O(13) C(5)–C(1) S(4)–C(5) C(3)–S(4) N(2)–C(3) C(1)–N(2)

Bond angles (°) 1.104 1.103 1.103 1.103 1.104 1.103 1.103 1.103 1.103 1.051 1.347 1.347 1.343 1.342 1.342 1.343 1.346 1.345 1.342 1.342 1.342 1.342 1.003 1.037 1.274 1.249 1.272 1.351 1.727 1.281 1.575 1.221 1.377 1.479 1.794 1.374 1.374

H(33)–C(20)–C(21) H(33)–C(20)–C(19) C(21)–C(20)–C(19) C(20)–C(19)–C(18) C(20)–C(19)–Cl(23) C(18)–C(19)–Cl(23) H(32)–C(18)–C(19) H(32)–C(18)–C(17) C(19)–C(18)–C(17) H(34)–C(21)–C(22) H(34)–C(21)–C(20) C(22)–C(21)–C(20) H(31)–C(17)–C(22) H(31)–C(17)–C(18) C(22)–C(17)–C(18) C(17)–C(22)–C(21) C(17)–C(22)–N(16) C(21)–C(22)–N(16) H(24)–N(16)–C(22) H(24)–N(16)–N(15) C(22)–N(16)–N(15) C(5)–S(4)–C(3) N(16)–N(15)–C(5) H(29)–C(10)–C(11) H(29)–C(10)–C(9) C(11)–C(10)–C(9) H(28)–C(9)–C(10) H(28)–C(9)–C(8) C(10)–C(9)–C(8) H(27)–C(8)–C(9) H(27)–C(8)–C(7) C(9)–C(8)–C(7) H(30)–C(11)–C(12) H(30)–C(11)–C(10) C(12)–C(11)–C(10) H(26)–C(7)–C(12) H(26)–C(7)–C(8) C(12)–C(7)–C(8) C(7)–C(12)–C(11) C(7)–C(12)–N(6) C(11)–C(12)–N(6) H(25)–N(6)–C(12) H(25)–N(6)–N(2) C(12)–N(6)–N(2) S(14)–C(3)–S(4) S(14)–C(3)–N(2) S(4)–C(3)–N(2)

Bond angles (°) 119.374 120.663 119.962 119.575 120.223 120.201 120.612 119.34 120.048 120.75 118.006 121.244 121.082 117.768 121.149 118.021 122.004 119.975 122.169 108.541 129.289 96.431 116.159 120.04 119.885 120.075 120.144 120.152 119.705 119.863 120.012 120.125 120.723 118.682 120.594 121.032 118.439 120.528 118.971 122.624 118.403 114.435 116.559 122.197 125.075 129.759 105.166

O(13)–H(24)–N(16) N(6)–N(2)–C(3) N(6)–N(2)–C(1) C(3)–N(2)–C(1) H(24)–O(13)–C(1) N(15)–C(5)–C(1) N(15)–C(5)–S(4) C(1)–C(5)–S(4) O(13)–C(1)–C(5) O(13)–C(1)–N(2) C(5)–C(1)–N(2) Dihedral angle (°) C(18)–C(17)–C(22)–N(16) C(20)–C(21)–C(22)–N(16) C(8)–C(7)–C(12)–N(6) C(10)–C(11)–C(12)–N(6) C(7)–C(12)–N(6)–N(2) N(15)–C(5)–C(1)–N(2)

154.955 125.246 123.92 110.827 108.971 116.366 131.251 112.383 115.007 129.797 115.194 −179.999 180 179.984 −179.986 −32.136 −179.659

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The colored precipitate, which formed immediately, was filtered and washed several times with water. The crude product was purified by recrystallization from hot ethanol [7]. The analytical data confirmed the expected compositions (Table 1). The ligands (Fig. 1) were also characterized by 1H NMR and IR spectroscopy. The resulting formed ligands are: HL1 = 5-(4′-methoxyphenylazo)-3-phenylamino-2thioxothiazolidin-4-one. HL2 = 5-(4′-methylphenylazo)-3-phenylamino-2-thioxothiazolidin4-one. HL3 = 5-(phenylazo)-3-phenylamino-2-thioxothiazolidin-4-one. HL4 = 5-(4′-chlorophenylazo)-3-phenylamino-2-thioxothiazolidin4-one. HL5 = 5-(4′-nitrophenylazo)-3-phenylamino-2-thioxothiazolidin4-one. 2.3. Preparation of Co(II) complexes All Co(II) polymer complexes were synthesized according to the general procedure [7]: a stoichiometric amount of the desired ligand

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(0.03 mol) in EtOH (20 cm3) was added dropwise to a hot EtOH solution (20 cm3) of Co(CH3COO)2·4H2O (0.02 mol) with stirring and the reaction mixture was refluxed for 3 h. The solution was concentrated to half of its original volume by evaporation and allowed to cool at room temperature. During this, a polycrystalline solid was separated, which was isolated by filtration, washed with EtOH, ether and dried in vacuo over anhydrous CaCl2. Formation of the polymer complexes (Fig. 2) can be obtainable in the following reaction: 2Co(CH3COO)2 . 4H2O + 3HLn → [(Co)2(Ln)2(HLn)(CH3COO)2(H2O)2]

2.4. Measurements Microanalytical data (C, H and N) were collected on Automatic Analyzer CHNS Vario ELIII, Germany. Spectroscopic data were obtained using the following instruments: FT-IR spectra (KBr disks, 4000– 400 cm−1) by Jasco FTIR-4100 spectrophotometer; the 1H-NMR spectra by Bruker WP 300 MHz using DMSO-d6 as a solvent containing TMS as the internal standard. X-ray diffraction analysis of compounds in powder forms was recorded on X-ray diffractometer in the range of diffraction angle 2θ = 4–80°. This analysis was carried out using CuKα

Table 6 The selected geometric parameters for HL5. Bond lengths (Å) C(21)–H(36) C(20)–H(35) C(18)–H(34) C(17)–H(33) C(11)–H(32) C(10)–H(31) C(9)–H(30) C(8)–H(29) C(7)–H(28) N(6)–H(27) C(17)–C(22) C(21)–C(22) C(20)–C(21) C(19)–C(20) C(18)–C(19) C(17)–C(18) C(7)–C(12) C(11)–C(12) C(10)–C(11) C(9)–C(10) C(8)–C(9) C(7)–C(8) H(23)–O(13) N(16)–H(23) C(22)–N(16) N(15)–N(16) C(12)–N(6) N(2)–N(6) C(19)–N(24) C(5)–N(15) C(3)–S(14) C(1)–O(13) C(5)–C(1) S(4)–C(5) C(3)–S(4) N(2)–C(3) C(1)–N(2) N(24)–O(26) N(24)–O(25)

Bond angles (°) 1.104 1.104 1.104 1.104 1.104 1.103 1.103 1.103 1.103 1.051 1.346 1.345 1.344 1.348 1.347 1.343 1.346 1.345 1.342 1.342 1.342 1.342 1.005 1.038 1.275 1.25 1.272 1.351 1.259 1.28 1.575 1.221 1.376 1.479 1.794 1.374 1.375 1.316 1.315

C(19)–N(24)–O(26) C(19)–N(24)–O(25) O(26)–N(24)–O(25) H(35)–C(20)–C(21) H(35)–C(20)–C(19) C(21)–C(20)–C(19) C(20)–C(19)–C(18) C(20)–C(19)–N(24) C(18)–C(19)–N(24) H(34)–C(18)–C(19) H(34)–C(18)–C(17) C(19)–C(18)–C(17) H(36)–C(21)–C(22) H(36)–C(21)–C(20) C(22)–C(21)–C(20) H(33)–C(17)–C(22) H(33)–C(17)–C(18) C(22)–C(17)–C(18) C(17)–C(22)–C(21) C(17)–C(22)–N(16) C(21)–C(22)–N(16) H(23)–N(16)–C(22) H(23)–N(16)–N(15) C(22)–N(16)–N(15) C(5)–S(4)–C(3) N(16)–N(15)–C(5) H(31)–C(10)–C(11) H(31)–C(10)–C(9) C(11)–C(10)–C(9) H(30)–C(9)–C(10) H(30)–C(9)–C(8) C(10)–C(9)–C(8) H(29)–C(8)–C(9) H(29)–C(8)–C(7) C(9)–C(8)–C(7) H(32)–C(11)–C(12) H(32)–C(11)–C(10) C(12)–C(11)–C(10) H(28)–C(7)–C(12) H(28)–C(7)–C(8) C(12)–C(7)–C(8) C(7)–C(12)–C(11) C(7)–C(12)–N(6) C(11)–C(12)–N(6) H(27)–N(6)–C(12) H(27)–N(6)–N(2) C(12)–N(6)–N(2)

Bond angles (°) 123.194 123.277 113.529 117.229 120.927 121.844 116.528 122.139 121.333 121.134 117.124 121.742 120.232 118.425 121.342 121.014 117.472 121.514 117.03 121.919 121.05 123.452 108.738 127.808 96.346 116.416 120.034 119.885 120.082 120.148 120.143 119.71 119.872 120.012 120.116 120.726 118.697 120.577 121.017 118.457 120.526 118.988 122.567 118.445 114.324 116.416 121.983

S(14)–C(3)–S(4) S(14)–C(3)–N(2) S(4)–C(3)–N(2) O(13)–H(23)–N(16) N(6)–N(2)–C(3) N(6)–N(2)–)–C(1) C(3)–N(2)–C(1) H(23)–O(13)–C(1) N(15)–C(5)–C(1) N(15)–C(5)–S(4) C(1)–C(5)–S(4) O(13)–C(1)–C(5) O(13)–C(1)–N(2) C(5)–C(1)–N(2) Dihedral angle (°) C(18)–C(17)–C(22)–N(16) C(20)–C(21)–C(22)–N(16) C(8)–C(7)–C(12)–N(6) C(10)–C(11)–C(12)–N(6) C(7)–C(12)–N(6)–N(2) N(15)–C(5)–C(1)–N(2)

125.137 129.758 105.104 154.405 125.155 123.876 110.964 108.934 116.031 131.371 112.597 115.476 129.532 114.989 −179.933 179.94 179.976 −179.978 −33.186 −179.523

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Fig. 4. The molecular structures (HOMO &LUMO) for HLn.

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Table 7 The calculated quantum chemical parameters for the ligands (HLn). Comp.

EHOMO (eV)

ELUMO (eV)

ΔE (eV)

χ (eV)

η (eV)

σ (eV)−1

Pi (eV)

S (eV)−1

ω (eV)

ΔNmax

HL1 HL2 HL3 HL4 HL5

−1.671 −1.907 −2.035 −1.614 −4.249

−0.333 −0.332 −0.332 −0.333 −0.004

1.338 1.575 1.703 1.281 4.245

1.002 1.1195 1.1835 0.9735 2.1265

0.669 0.7875 0.8515 0.6405 2.1225

1.49476831 1.26984127 1.17439812 1.56128025 0.47114252

−1.002 −1.1195 −1.1835 −0.9735 −2.1265

0.74738416 0.63492063 0.58719906 0.78064012 0.23557126

0.75037668 0.79573349 0.82247343 0.7398144 1.06525377

1.49775785 1.4215873 1.38990018 1.51990632 1.00188457

radiation (λ = 1.540598 Ả). The applied voltage and the tube current are 40 KV and 30 mA, respectively. Mass spectra were recorded by the EI technique at 70 eV using MS-5988 GS-MS Hewlett-Packard. UV– Visible spectra by Perkin-Elmer AA800 spectrophotometer Model AAS. Thermal analysis of the ligands and their Co (II) complexes was carried out using a Shimadzu thermogravimetric analyzer under a nitrogen atmosphere with heating rate of 10 °C/min over a temperature range from 30 °C up to 800 °C. Magnetic susceptibility measurements were determined at room temperature on a Johnson Matthey magnetic susceptibility balance using Hg[Co(SCN)4] as calibrate. Conductivity measurements of the complexes at 25 ± 1 °C were determined in DMF (10−3 M) using conductivity/TDS meter model Lutron YK-22CT. The molecular structures of the investigated compounds were optimized by HF method with 3-21G basis set. The molecules were built with the Perkin Elmer ChemBio Draw and optimized using Perkin Elmer ChemBio3D software [18,19]. 2.5. DNA binding experiments The binding properties of the ligands and their complexes to SS-DNA have been studied using electronic absorption spectroscopy. SS-DNA (50 mg) was dissolved by stirring overnight in double deionized water (pH = 7.0) and kept at 4 °C. Doubly distilled water was used to prepare buffers (20 mM phosphate buffer (NaH2PO4–Na2HPO4), pH = 7.2). A solution of (SS-DNA) in the buffer gave a ratio of UV absorbance at 260 and 280 nm (A260/A280) of ca. 1.8, indicating that the DNA was sufficiently free of protein [20]. The DNA concentration was determined by UV absorbance spectroscopy using the molar absorption coefficient of 6600 M−1 cm−1 at 260 nm for SS-DNA [21,22] and was found to be 1.4 × 10−4. Electronic absorption spectra (200–900 nm) were carried out using 1 cm quartz cuvette at 25 °C by fixing the concentration of ligand (1.00 × 10−3 mol.L−1), while gradually increasing the concentration of SS-DNA (0.00 to 1.30 × 10−4 mol.L− 1). An equal amount of SS-DNA was added to both the compound solutions and the references

buffer solution to eliminate the absorbance of SS-DNA itself. The intrinsic binding constant Kb of the compound with SS-DNA was determined using the following Eq. (1) [23]:


 ½DNA= єa –є f ¼ ½DNA= єb –є f þ 1=K b єa –є f

ð1Þ

where [DNA] is the concentration of SS-DNA in base pairs, єa is the extinction coefficient observed for the Aobs/[compound] at the given DNA concentration, єf is the extinction coefficient of the free compound in solution and єb is the extinction coefficient of the compound when fully bond to DNA. In plots of [DNA] / (єa − єf) vs. [DNA], Kb is given by the ratio of the slope to the intercept. 2.6. Cytotoxicity investigation 2.6.1. Cell lines and chemical reagents Hepatocellular carcinoma (HePG-2) and mammary gland breast cancer (MCF-7) cell lines were obtained from ATCC via Holding company for biological products and vaccines (VACSERA), Cairo, Egypt. Chemical reagents; RPMI-1640 medium, MTT, DMSO and 5-fluorouracil were purchased from Sigma chemicals (St. Louis, USA), Fetal Bovine serum (FBS) was purchased from (GIBCO, UK). 5-fluorouracil (5-FU) was used as a standard anticancer drug for comparison. 2.6.2. MTT assay The cell lines mentioned above were used to determine the inhibitory effects of ligands and their Co(II) complexes on cell growth using the MTT assay [24]. This colorimetric assay is based on the conversion of the yellow tetrazolium bromide (MTT) to a purple formazan derivative by mitochondrial succinate dehydrogenase in viable cells. Cell lines were cultured in RPMI-1640 medium with 10% fetal bovine serum. Antibiotics added were 100 units/ml penicillin and 100 μg/ml streptomycin at 37 °C in a 5% CO2 incubator. The cell lines were seeded in a 96-well plate at a density of 1.0 × 104 cells/well at 37 °C for 48 h under 5% Co2, followed by 24 h incubation with the indicated drug doses [25]. In the end of the drug treatment, 20 μl of MTT solution at 5 mg/ml was added and incubated for 4 h. Dimethyl sulfoxide (DMSO) in volume of 100 μl is added into each well to dissolve the purple formazan formed. The colorimetric assay is measured and recorded as absorbance at 570 nm using a plate reader (EXL 800). Cytotoxicity was expressed as

Table 8 IR data (cm−1) of free ligands (HLn) and their Co(II) complexes (1–5).

Fig. 5. The relation between Hammett's substitution coefficients (σR) vs. energy gap (ΔE).

a

Compound

υ(NH)

υ(C = O)

υ(C = S)

υ(Co-O)

υ(Co-N)

υ(Co-S)

HL1 (1) HL2 (2) HL3 (3) HL4 (4) HL5 (5)

3207 – 3205 – 3209 – 3207 – 3210 –

1751 1722 1754 1718 1727 1725 1751 1724 1735 1716

881 825 882 815 842 815 823 819 846 844

– 680 – 684 – 690 – 690 – 680

– 528 – 590 – 598 – 580 – 590

– 485 – 488 – 499 – 498 – 480

Numbers as given in Table 1.

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IC50 (μg/mL) which indicates the concentration of the compound that inhibited proliferation rate of the tumor cells by 50% as compared to the control untreated cells. IC50 values were determined from the plot: % relative cell viability (% inhibition concentration) vs. compound concentration. The relative cell viability values were calculated as follows: %The relative cell viability ¼

A ð570 nmÞ of treated samples  100 A ð570 nmÞ of untreated sample

sample was run without ABTS and using MeOH/phosphate buffer (1:1) instead of tested compounds. L-ascorbic acid was used as standard antioxidant (positive control) and the negative control was run with ABTS and MeOH/phosphate buffer (1:1) only.

%Inhibition ¼

A ðcontrolÞ−A ðtestÞ  100 A ðcontrolÞ

2.8. Antimicrobial investigation 2.7. Antioxidant investigation Antioxidant activity screening assay ABTS method [26–28] used for determination of scavenging activity of ligands (HLn) and their Co(II) complexes (1–5). For each of the investigated compounds (2 mL) of ABTS (2,2′-azinobis-(3-ethyl-benzothiazoline-6-sulphonic acid) solution (60 μM) was added to 3 mL MnO2 solution (25 mg/mL), all prepared in (5 mL) aqueous phosphate buffer solution (pH 7, 0.1 M). The mixture was shaken, centrifuged, filtered and the absorbance of the resulting green blue solution (ABTS free radical solution) at 734 nm was adjusted to approx. ca. 0.5. Then, 50 μl of (2 mM) solution of the tested compound in spectroscopic grade MeOH/phosphate buffer (1:1) was added. The absorbance was measured and the reduction in color intensity was expressed as inhibition percentage (I %). Blank

Rhodanine compounds were individually tested against Gram negative (Escherichia coli) bacteria, Gram positive (Staphylococcus aureus) and yeast (Candida albicans). Each of the compounds was dissolved in DMSO and solutions of the concentration 1 mg/ml were prepared separately and paper disks of Whatman filter paper were prepared with standard size (5 cm) and sterilized in an autoclave. The paper disks were soaked in the desired concentration of the complex solution and were placed aseptically in the petri dishes containing nutrient agar media (agar 20 g, beef extract 3 g and peptone 5 g) seeded with Staphylococcus aureus, E. coli and Candida albicans. The petri dishes were incubated at 36 °C and the inhibition zones were recorded after 24 h of incubation. Each treatment was replicated three times. The antibacterial activity of a common standard antibiotic ampicillin and

Fig. 6. X-ray diffraction patterns for ligands (HL1, HL3 and HL4) and the complex (1) in powder forms.

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Fig. 7. a. Mass spectrum of HL1. b. Mass spectrum of HL3. c. Mass spectrum of HL4.

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antifungal colitrimazole was also recorded using the same procedure as above using the same concentration and solvents. The % activity index for the complex was calculated by the formula: %Activity Index ¼

Zone of inhibition by test compound ðdiameterÞ  100 Zone of inhibition by standard ðdiameterÞ

3. Results and discussion 3.1. Molecular structure The molecular structures of the ligands (HLn) were optimized by HF method with 3-21G basis set. The molecules were built with the Perkin Elmer ChemBioDraw and optimized using Perkin Elmer ChemBio3D software. The geometrical parameters bond lengths and bond angles of HLn are calculated and presented in Fig. 3 and Tables 2–6. Molecular

structures (HOMO &LUMO) for HLn are presented in Fig. 4. The HOMO– LUMO energy gap, ΔE, which is an important stability index, is applied to develop theoretical models for explaining the structure and conformation barriers in many molecular systems. The smaller the value of ΔE is, the more the stability the compound has [3,18]. The calculated quantum chemical parameters are given in Table 7. Additional parameters such as separation energies, ΔE, absolute electronegativities, χ, chemical potentials, Pi, absolute hardness, η, absolute softness, σ, global electrophilicity, ω [29], global softness, S, and additional electronic charge, ΔNmax, have been calculated according to the following Eqs. (2–9): ΔE ¼ ELUMO −EHOMO

χ¼

−ðEHOMO þ ELUMO Þ 2

a)

b)

c) Scheme 1. a. Fragmentation patterns of HL1. b. Fragmentation patterns of HL3. c. Fragmentation patterns of HL4.

ð2Þ

ð3Þ

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Fig. 9. TGA curves of complexes (1–5). Fig. 8. TGA curves of ligands HL

ELUMO −EHOMO η¼ 2

ð4Þ

σ ¼ 1=η

ð5Þ

Pi ¼ −χ

ð6Þ

Table 10 Thermal analysis data of the complexes (1–5). Complexa

Temp. range (°C)

Found mass loss (calc.) %

Assignment

(1)

0–140 140–510 510–800 N800 0–145 145–505 505–800 N800 0–160 160–550 550–800 N800 0–155 155–515 515–800 N800 0–155 155–525 525–800 N800

11.4 (11.45) 50.49 (50.75) 26.41(26.64) 11.7 (11.15) 11.19 (11.88) 50.95 (50.15) 25.9 (26.39) 11.96 (11. 56) 11.97 (12.27) 49.73 (49.6) 25.8(26.15) 12.8 (11.95) 11.42 (11.34) 50.36 (50.9) 26.4(26.7) 11.82 (11.04) 11.03 (11.08) 51.33 (51.26) 26.28(26.85) 10.36 (10.7)

Loss of C4H10O6. Loss of C32H26N8O2S4. Loss of C16H14N4O2S2. Loss of 2CoO Loss of C4H10O6. Loss of C32H26N8S4. Loss of C16H14N4OS2. Loss of 2CoO Loss of C4H10O6. Loss of C30H22N8S4. Loss of C15H12N4OS2. Loss of 2CoO Loss of C4H10O6. Loss of C30H20N8S4Cl2. Loss of C15H11N4OS2Cl. Loss of 2CoO Loss of C4H10O6. Loss of C30H20N10O4S4. Loss of C15H11N5O3S2. Loss of 2CoO

(2)

1 2η

ð7Þ

ω ¼ Pi2 =2η

ð8Þ

ΔN max ¼ −Pi=η

ð9Þ

S¼

The value of ΔE for ligands HL1, HL2, HL3, HL4 and HL5 was found 1.338, 1.575, 1.703, 1.281 and 4.245 eV, respectively. The calculations indicated that the HL4 is more stable form than the other ligands [3].The relation between Hammett's substitution coefficients (σR) vs. energy gap (ΔE) is shown in Fig. 5. It is clear that that the values increase with increasing σR.

(3)

(4)

(5)

a

Numbers as given in Table 1.

3.2. Metal complexes The interaction of hydrazone ligands (HLn) with [Co(CH3COO)2].4H2O in a molar ratio 2:3 [Co:HLn] under reflux conditions gave the polymeric products presented in Table 1. The polymeric Co(II) complexes are stable in air and soluble in DMF and DMSO. The molar conductance values for the cobalt (II) complexes (10−3 M) are measured in DMF at 25 °C and

these values are in the range of 4–12 Ω−1 cm2 mol−1 indicating a nonelectrolytic nature [23]. The no electrolytic nature of the Co(II) polymeric complexes implies the contribution of acetate ions to the coordination sphere in the complexes under investigation.

Table 9 Thermal analysis data of the ligands (HLn). Compound HL1

HL2 HL3 HL4 HL5

Temp. range (°C)

Found mass loss (calc.) %

Assignment

30–260 260–570 570–800 30–265 265–700 700–800 30–330 330–800 30–350 350–800 30–400 400–600 600–800

62 (61.9) 30 (29.6) 8 (8.6) 65 (64.9) 30 (30.9) 5 (4.3) 68 (67.7) 32 (32.3) 71 (71.3) 29 (28.9) 59 (59.5) 28 (28.4) 13 (12.3)

Decomposition of a part of the ligand (C9H6N2S2O). Further decomposition of a part of the ligand (C6H6N2). Further decomposition of a part of the ligand (OCH3). Decomposition of a part of the ligand (C9H6N2S2O). Further decomposition of a part of the ligand (C6H6N2). Further decomposition of a part of the ligand (CH3). Decomposition of a part of the ligand (C9H6N2S2O). Further decomposition of a part of the ligand (C6H6N2). Decomposition of a part of the ligand (C9H7N2S2OCl). Further decomposition of a part of the ligand (C6H5N2). Decomposition of a part of the ligand (C9H6N2S2O). Further decomposition of a part of the ligand (C6H6N2). Further decomposition of a part of the ligand (NO2).

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Evidence for all polymeric nature comes from its solubility properties and the metal polymer complex to ligand stoichiometry which is shown to be 2:3 from the elemental analysis. IR spectroscopy provides partial evidence that the ligand is acting as a bridge, and that bridging occurs through both the S and NH from side and through O and N (hydrazone) from the other side.

3.3. Infrared spectra and nature of coordination The three bands around 823–882, 3205–3210 and 1727–1754 cm−1 in the ligands assigned to υ(CS), –NH(3-phenylamine) and υ(CO) groups, respectively, were shifted to lower frequencies and –NH(3phenylamine) disappearance in all polymer complexes. This indicates

Fig. 10. Coats–Redfern (CR) of ligands (HLn), Stages (I, II).

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725

Fig. 10 (continued).

the participation of the thione sulfur, NH(3-phenylamine) and carbonyl oxygen groups, in the chelation (Table 8) [30]. The splitting of υ(N=N) band into two bands in the ranges 1435–1520 and ~1230 cm−1 due to υ(HC=N) and υ(=N–NH) hydrazone, respectively, for ligands provides an evidence that the hydrazone N participate in the chelation after deprotonation leading to a covalent linkage. This is more rather confirmed from the observation of Karabatoses et al. [31] and El-Sonbati et al. [32] where the hydrazone form is more than the azo structure for similar compounds (Fig. 1D). In all polymer complexes, CN group remained intact, indicating the non-participation of the azomethine nitrogen in the chelation [33]. The strong observed at ~1111–1123 cm−1 may be assigned to υ(N–N) vibration mode [34] is affected on complexation. It is blue shifted and appearance as a weak band. In all polymer complexes, there are two bands υas(1427–1444) and υs(1230–1243) cm−1 stretching vibration of acetate group. The correlation between the positions of the antisymmetric and symmetric stretching vibration of this group was earlier studied [35]. It was concluded from these studies that the frequency difference between the two carbonyl stretches of ionic acetate groups is usually in the interval ~160 cm−1, longer values were found for monodentate and lower values for bidentate groups [36]. Correspondingly, the split of 195–201 cm−1 in polymer complexes indicates monodentate acetate. This is supported by results of Ryde [37].

The above interpretation is further supported by the appearance of the non-ligand bands at: 680–690 cm−1; υ(Co–O), 528–598 cm−1; υ(Co–N) [38] and 480–500 cm− 1; υ(Co–S) [39]. Such class of compounds is with different types of hydrogen bonding [2–6]: 1. H-bonding of the type NH⋯O between the –NH (hydrazone) group and C=O group. 2. Intermolecular hydrogen bonding of the NH⋯O type of one molecule to another one. 3. The case is more favored. This is due to the presence of a broad band located at 870–965 cm−1 which could be taken as a good evidence for the intermolecular hydrogen bonding. In all polymer complexes ~ 3500–3200 cm− 1 is observed, such region is attributed to different probabilities: (i) it is due to either free OH or NH, (ii) bonded –OH group or –NH group or (iii) due to the presence of coordinated water molecules. 3.4. 1H NMR spectra The 1H NMR spectra of the ligands are recorded in dimethylsulfoxide (DMSO-d6) solution using tetramethylsilane (TMS) as internal standard. The broad signal exhibited by the ligands can be assigned to

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intramolecular hydrogen bonded proton of NH (hydrazone) at ∼11.5 ppm and NH(3-phenylamine) at ∼9.0 ppm were not affected by dilution and disappear in the presence of D2O. The chemical shifts of the different types of protons in the 1H NMR spectra of the ligands

(HL1 and HL2) display sharp signals at 3.7 and 2.3 ppm with an integration equivalent to three hydrogens corresponding to the O–CH3 and C– CH3 groups, respectively. The aromatic rings give a group of multi signals at 6.5–8.0 ppm.

Fig. 11. Coats–Redfern (CR) of Co(II) complexes (1–5), Stages (I, II).

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727

Fig. 11 (continued).

The 13C NMR of ligands exhibited signals at 170 _172 ppm corresponding to the carbon of (C=N) groups, signals appear at 160– 163 ppm corresponding to (C=O) groups and signals around ~200 ppm corresponding to the carbon of (C=S). Ligands have different chemical shift due to aromatic ring substituent. Therefore, it is clear from these results that the data obtained from the elemental analyses; IR and 1H NMR spectra measurements are in agreement with each other. 3.5. X-ray diffraction analysis The X-ray diffraction (XRD) patterns of HL1, HL3 and HL4 ligands and complex (1) in powder forms are shown in Fig 6. The XRD patterns of HL1, HL3 and HL4 ligands show many sharp diffraction peaks in addition to a broad hump at 2θ = 8°. This behavior indicates that the powder is a mixture of amorphous and polycrystalline nature. The XRD pattern of complex (1) shows amorphous nature.

fragmentation mode of ligand (HL1) shows the exact mass of 358 corresponding to the formula C16H14N4O2S2 (Fig. 7a). The ion of m/z = 358 undergoes fragmentation to a stable peak at m/z = 224 by losing C7H7N2O atoms (structure I) as shown in Scheme (1a). A breakdown of the backbone of HL1 ligand gives the fragment (structure II) with m/z = 77 by losing of C3H2N2OS2. The mass spectrum fragmentation mode of ligand (HL3) shows the exact mass of 328 corresponding to the formula C15H12N4OS2 (Fig. 7b). The ion of m/z = 328 undergoes fragmentation to a stable peak at m/z = 224 by losing C6H5N2 atoms (structure I) as shown in Scheme (1b). A breakdown of the backbone of HL3 ligand gives the fragment (structure II) with m/z = 77 by losing of C3H2N2OS2. The mass spectrum fragmentation mode of ligand (HL4) shows the exact mass of 362.5 corresponding to the formula C15H11N4OS2Cl (Fig. 7c). The ion of m/z = 362 undergoes fragmentation to a stable peak at m/z = 224 by losing C6H4N2Cl atoms (structure I) as shown in Scheme (1c). A breakdown of the backbone of HL4 ligand gives the fragment (structure II) with m/z = 77 by losing of C3H2N2OS2.

3.6. Mass spectra 3.7. Electronic spectra and magnetic measurements The mass spectra of ligands (HL1, HL3 and HL4) are recorded and investigated at 70 eV of electron energy. It is obvious that, the molecular ion peaks are in good agreement with their suggested empirical formula as indicated from elemental analyses (Table 1). The mass spectrum

The electronic absorption spectra of the two ligands (HLn) exhibits bands at 26,350–26,150 cm− 1 (CS) (n → π*), 30,460–30,250 cm−1 (CO) (n → π*), 32,980–33,100 cm− 1 (H-bonding and association),

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40,240–39,890 cm− 1 (phenyl) (ph-ph*, π–π*) [40] and 29,610– 29,350 cm− 1 transition of phenyl rings overlapped by composite broad π–π* of azo/CH=N structure. In the Co(II) complexes, the (CS and CO) (n–π*) transition shifts to lower energy. These shifts or the

disappearance of the bands are indicative of coordination of the ligands are indicative of coordination of the ligands to Co(II). Based on magnetic moment values, the cobalt(II) compounds fall into two classes. In the first, the so called ionic complexes are with μeff

Fig. 12. Horowitz–Metzger (HM) of ligands (HLn), stages (I, II).

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729

Fig. 12 (continued).

values lying in the first range 4.3–5.6 B.M., while the second is with much smaller values (1.7–2.9 B.M.) and are of covalent properties. From such scope of representation, the first class of cobalt(II) complexes. (i) may be associated with low spin octahedral field, while the second class (ii) is of square planar environment around cobalt(II). The spectra of our data exhibited bands located at 9200–2210 and 43,320–4400 cm− 1. Such finding is a strong indicative of octahedral spatial configuration. It is of interest to mention that the low magnetic moments of Co(II) complexes (μeff. = 1.15–1.24 B.M./atom) could be referred to occur through a ligand bridge as shown in Fig. 2. Another reason for the lowering magnetic moments may be due to the admixture of cobalt(II) and cobalt(III) ions in the same molecule. 3.8. Thermal analysis The TGA curves for the ligands (HLn) are shown in Fig. 8. It is clear that the change of substituent affects the thermal properties of the ligands. The temperature intervals and the percentage of loss of masses are listed in Table 9. HL1 ligand shows three decomposition steps, the first stage that occurs in the temperature range 30–260 °C is attributed to loss of C9H6N2S2O (found 62.0% and calc. 61.9%). The second stage in the temperature range 260–570 °C corresponds to loss of a part of the ligand

(C6H6N2) (Found 30.0%, calc. 29.6%). The third stage in the temperature range 570–800 °C corresponds to loss of a part of the ligand (OCH3) (Found 8.0%, calc. 8.6%). HL2 ligand shows three decomposition steps, the first stage that occurs in the temperature range 30–265 °C is attributed to loss of (C9H6N2S2O) (found 65.0% and calc. 64.9%). The second stage in the temperature range 265–700 °C corresponds to loss of a part of the ligand (C6H6N2) (found 30.0%, calc. 30.9%). The third stage in the temperature range 700–800 °C corresponds to loss of a part of the ligand (CH3) (Found 5.0%, calc. 4.3%). HL3 ligand shows two decomposition steps, the first stage that occurs in the temperature range 30–330 °C is attributed to loss of (C9H6N2S2O) (found 68.0% and calc. 67.7%). The second stage in the temperature range 330–800 °C corresponds to loss of a part of the ligand (C6H5N2) (found 32.0%, calc. 32.3%). HL4 ligand shows two decomposition steps, the first stage that occurs in the temperature range 30–350 °C is attributed to Loss of (C9H7N2S2OCl) (found 71.0% and calc. 71.3%). The second stage in the temperature range 350–800 °C corresponds to loss of a part of the ligand (C6H5N2) (found 29.0%, calc. 28.9%). HL5 ligand shows three decomposition steps, the first stage that occurs in the temperature range 30–400 °C is attributed to Loss of (C9H6N2S2O) (found 59.0% and calc. 59.5%). The second stage in the

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temperature range 400–600 °C corresponds to loss of a part of the ligand (C6H6N2) (found 28.0%, calc. 28.4%). The third stage in the temperature range 700–800 °C corresponds to loss of a part of the ligand (NO2) (found 13.0%, calc. 12.3%).

The TGA curves for Co(II) complexes (1–5) are shown in Fig. 9. The temperature intervals and the percentage of loss of masses are listed in Table 10. The TG curves of all Co (II) complexes (1–5) showed the loss of C4H10O6 in the temperature range ~30–150 °C. The first stage is

Fig. 13. Horowitz–Metzger (HM) of Co(II) complexes (1–5), stages (I, II).

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731

Fig. 13 (continued).

Table 11 Thermodynamic data of the thermal decomposition of ligands (HLn). Parameter Compound

Decomposition temperature (°C)

211–346 HL1 498–624 158–401 HL2 502–643 225–271 HL3 443–630 142–240 HL4 301–418 127–372 HL5 496–715

Method

Ea (kJ mol−1)

A (s−1)

ΔS⁎ (J mol−1 K−1)

ΔH⁎ (kJ mol−1)

ΔG⁎ (kJ mol−1)

R

CR HM CR HM CR HM CR HM CR HM CR HM CR HM CR HM CR HM CR HM

45.8 53.6 180 193 46.9 48.4 162 173 329 338 108 120 70.9 80.8 102 114 31.2 39.2 108 119

7.58 × 101 4.18 × 102 4.43 × 108 6.40 × 109 7.11 × 101 1.17 × 102 2.34 × 107 2.50 × 108 2.54 × 1030 1.70 × 1032 1.51 × 104 2.05 × 105 5.53 × 105 1.40 × 107 1.31 × 106 2.10 × 107 3.31 × 100 3.59 × 101 1.59 × 104 5.78 × 104

−214 −200 −87.9 −65.8 −215 −210 −113 −92.2 333 367 −173 −152 −139 −112 −134 −111 −240 −220 −173 −163

41.2 49 174 186 42.3 43.8 155 166 325 333 101 113 67.1 76.9 96.5 108 26.9 34.9 101 112

159 159 247 241 161 160 250 245 151 142 242 236 131 129 181 179 152 150 254 255

0.99221 0.99398 0.99355 0.99169 0.99322 0.99788 0.98442 0.99156 0.99453 0.99452 0.99432 0.9939 0.99122 0.98595 0.99104 0.99064 0.99523 0.98744 0.98712 0.98669

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Table 12 Thermodynamic data of the thermal decomposition of Co(II) complexes (1–5). Parameter Compounda

Decomposition temperature (°C)

140–510 (1) 510–545 140–505 (2) 505–540 150–500 (3) 500–550 155–515 (4) 515–540 155–500 (5) 500–550 a

Method

Ea (kJ mol−1)

A (s−1)

ΔS⁎ (J mol−1 k−1)

ΔH⁎ (kJ mol−1)

ΔG⁎ (kJ mol−1)

R

CR HM CR HM CR HM CR HM CR HM CR HM CR HM CR HM CR HM CR HM

10.6 19.4 722 734 11.4 21.7 691 726 14.8 25 412 430 6.76 18.6 744 740 8 18.1 367 377

6.31 × 103 5.36 × 102 2.20 × 1045 1.88 × 1046 6.47 × 103 9.87 × 102 4.44 × 1043 1.14 × 1046 1.43 × 102 2.14 × 101 6.11 × 1024 1.77 × 1026 1.35 × 103 3.95 × 102 8.17 × 1046 5.05 × 1046 2.51 × 103 3.83 × 102 1.50 × 1022 5.83 × 1022

−293 −275 615 633 −293 −270 583 629 −286 −264 221 249 −306 −278 645 641 −301 −278 171 183

5.59 14.4 715 727 6.41 16.8 684 719 9.81 20 406 423 1.70 13.5 738 734 3.01 13.1 360 371

181 179 223 221 181 177 221 220 181 178 229 224 188 182 221 221 183 180 223 225

0.96357 0.94125 0.97664 0.99571 0.9262 0.9493 0.98464 0.98183 0.9478 0.93629 0.99286 0.99395 0.92499 0.90661 0.98471 0.97099 0.9166 0.93422 0.92419 0.93396

Numbers as given in Table 1.

related to loss of the part of the deprotonated ligand. The second stage is related to loss of HLn. The final weight losses are due to the decomposition of metal oxides residue (Table 10). 3.8.1. Calculation of activation thermodynamic parameters The thermodynamic activation parameters of decomposition processes of the ligands HLn and their Co(II) complexes (1–5) namely activation energy (Ea), enthalpy (ΔH*), entropy (ΔS*), and Gibbs free energy change of the decomposition (ΔG*) are evaluated graphically by employing the Coast–Redfern [41] and Horowitz–Metzger [42] methods. 3.8.1.1. Coast–Redfern equation. The Coast–Redfern equation, which is a typical integral method, can represent as: Z

α 0

dx A ¼ ð1−α Þn ϕ

Z

T2 T1

  Ea dt exp − RT

ð11Þ

# 1−ð1−α Þ1−n Ea θ ¼ ; for n≠1 log 1−n 2:303RT 2s

ð13Þ

when n = 1, the LHS of Eq. (13) would be log[−log(1-α)] (Figs. 12 and 13). For a first order kinetic process, the Horowitz–Metzger equation may write in the form:    Wα Ea θ log log ¼ − log2:303 Wγ 2:303RT 2s

ð14Þ

where θ = T − Ts, wγ = wα − w, wα = mass loss at the completion reaction; w = mass loss up to time t. The plot of log [log (wα/wγ)] vs. θ was drawn and found to be linear from the slope of which Ea was calculated. The pre-exponential factor, A, is calculated from equation:

Ea RT 2s

A plot of left-hand side (LHS) against 1/T was drawn (Figs. 10 and 11). Ea is the energy of activation and calculated from the slope and A in (s− 1) from the intercept value. The entropy of activation (ΔS⁎) in (Jmol−1 K−1) is calculated by using the equation:   Ah R ΔS ¼ 2:303 log kB T s

"

ð10Þ

For convenience of integration, the lower limit T1 is usually taken as zero. This equation on integration gives     ln ð1−α Þ Ea AR ¼ − þ ln ln − RT ϕEa T2

3.8.1.2. Horowitz–Metzger equation. The Horowitz–Metzger equation is an illustrative of the approximation methods. These authors derived the relation:



ð12Þ

Where kB is the Boltzmann constant, h is the Plank's constant and Ts is the TG peak temperature.

A   ¼ Ea ϕ exp − RT s

ð15Þ

The entropy of activation, ΔS⁎, is calculated from Eq. (12). The enthalpy activation, ΔH⁎, and Gibbs free energy, ΔG⁎, is calculated from: ΔH  ¼ Ea −RT

ð16Þ

ΔG ¼ ΔH  −TΔS

ð17Þ

The calculated values of Ea, A, ΔS⁎, ΔH⁎ and ΔG⁎ for the decomposition steps for ligands (HLn) and cobalt(II) complexes (1–5) are summarized in Tables 11 and 12.

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Fig. 14. Absorption spectra of ligands (HLn) in buffer pH 7.2 at 25 °C in the presence of increasing amount of SS-DNA. Arrows indicate the changes in absorbance upon increasing the SS-DNA concentration. Inset: plot of [DNA] / (εa − εf) M2 cm vs. [DNA] M for titration of DNA with ligands (HLn).

3.9. Stoichiometries of the cobalt(II) complexes Analytical data of the polymeric complexes (Table 1) were isolated in the general formulae [(Co)2(Ln)2(HLn)(CH3COO)2(OH2)2]n as shown in Fig. 2. The 2:3 stoichiometries of the polymeric complexes were calculated from their elemental analyses. The analytical data and the molar conductance measurements of the polymeric

complexes reveal that three molecules of the ligand and two of the anions are coordinated to the two metal atoms in all complexes. The ligands present four donor sites: the azo nitrogen, the carbonyl oxygen and the thionyl sulfur of rhodanine moiety and the NH group of 3-phenylamino. However, it is clear that the utilization of all the four bonding sites would introduce certain steric restrictions and hence either both the azo nitrogen and the carbonyl group

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Fig. 15. The relation between Hammett's substitution coefficients (σR) vs. intrinsic binding constants (Kb) of the ligands (HLn).

would coordinate or the NH group and the carbonyl group would coordinate. The coordination of NH group and carbonyl group seems unlikely in view of the large size of the chelated ring. Polymeric complexes do not have a sharp melting point and decompose at higher temperature.

3.10. DNA binding studies 3.10.1. Electronic absorption measurements Absorption titration is one of the most universally employed methods to study the binding modes and binding extent of compounds to DNA. Absorption titration experiments were performed with fixed concentrations of the ligands (HLn) (30 μM) while gradually increasing the concentration of DNA (10 mM) at 25 °C. While measuring the absorption spectra, an equal amount of DNA was added to both the compound solution and the reference solution to eliminate the absorbance of DNA itself. We have determined the intrinsic binding constant to SS-DNA by monitoring the absorption intensity of the charge transfer spectral bands near 470, 455, 437, 480 and 540 nm for the ligands (HL1 −HL5), respectively. The absorption spectra of these ligands with increasing concentration of SS-DNA in the range 300–700 nm are shown in Fig. 14.

DNA interaction study by UV–Visible Spectroscopy Electronic absorption spectra was initially used to examine the interaction between ligands (HLn) and SS-DNA. After interaction with increasing amount of DNA, all the peaks decreased gradually and the wavelengths have minor red shift of 1–2 nm. Long and Barton [43] had pointed out that the absorption peaks shift of the small molecules after they interacted with DNA could be as the clues to judge the binding mode between the small molecules and DNA: If the binding involves a typical intercalative mode, a hypochromism effect coupled with obvious bathochromism for the characteristic peaks of the small molecules will be found due to the strong stacking between the chromophore and the base pairs of DNA [44]. Therefore, based on this viewpoint, the interaction between ligands (HLn) and SS-DNA could be noncovalent intercalative binding. After intercalating the base pairs of DNA, the π* orbital of the intercalated ligand could couple with π orbital of base pairs, thus decreasing the π–π* transition energy, and further resulting in the bathochromism. On the other hand, the coupling of a π orbital with partially filled electrons decreases the transition probabilities hence results hypochromic shift. Since hypochromism due to π–π* stacking interactions may appear in the case of the intercalative binding mode, while bathochromism (red-shift) may be observed when the DNA duplex is stabilized [45,46]. The intrinsic binding constants (Kb) of all the ligands (HLn) with SS-DNA were determined (Eq. 1) [47]. The Kb values obtained from the absorption spectral technique for ligands (HL1 −HL5) were calculated as 2.63 × 105, 3.15 × 105, 4.64 × 105, 5.1 × 105 and 7.35 × 105 M−1, respectively. The values of binding constant are related to the nature of the p-substituent as they increase according to the following order p-(NO2 N Cl N H N CH3 N OCH3). This can be attributed to the fact that the effective charge increased due to the electron withdrawing psubstituent (HL4 and HL5) while it decreased by the electrons donating character of (HL1 and HL2). This is in accordance with that expected from Hammett's constant (σR) as shown in Fig. 15, correlate the binding constant values with σR it is clear that all these values increase with increasing σR. 3.11. Cytotoxic activity The synthesized ligands (HLn) and their Co(II) complexes (1–5) have been evaluated for in vitro cytotoxic activity against two human cancer cell lines; HePG-2 (Hepatocellular carcinoma) and MCF-7 (breast cancer). Inhibitory activity against HePG-2 and MCF-7 cell lines was detected by using different concentrations (i.e., 50, 25, 12.5, 6.25, 3.125, 1.56, and 0 μg) of the tested compounds and viability cells (%) were determined by the colorimetric method, data presented in Table 13. Also,

Table 13 Evaluation of cytotoxicity of ligands (HLn) and their Co(II) complexes (1–5) against HePG-2 and MCF-7 cells. Compound cell lines

Sample conc.

HePG-2

100 μg/ml 50 μg/ml 25 μg/ml 12.5 μg/ml 6.25 μg/ml 3.125 μg/ml 1.56 μg/ml 0 μg/ml 100 μg/ml 50 μg/ml 25 μg/ml 12.5 μg/ml 6.25 μg/ml 3.125 μg/ml 1.56 μg/ml 0 μg/ml

MCF-7

5-FU

HL1

HL2

HL3

HL4

HL5

(1)

(2)

(3)

(4)

(5)

8.6 17.1 24.0 33.1 56.8 70.6 88.7 100 5.8 10.3 16.2 28.5 48.4 62.8 81.6 100

8.3 15.6 21.9 36.7 55.4 74.3 92.6 100 24.0 30.8 42.7 54.9 69.3 88.1 100 100

7.9 15.6 24.3 38.4 56.7 78.1 95.5 100 34.6 46.5 59.2 68.4 83.3 98.5 100 100

7.5 14.2 20.8 34.6 47.1 58.3 76.4 100 7.9 13.4 20.0 31.5 50.3 61.7 74.6 100

7.6 14.3 22.0 35.3 54.7 73.5 90.5 100 20.1 27.2 39.5 51.3 72.8 93.4 100 100

13.1 18.8 26.4 37.2 67.5 75.9 96.9 100 28.3 39.1 52.0 63.7 77.2 96.3 100 100

30.4 42.8 53.9 66.2 87.5 99.1 100 100 48.1 60.0 72.8 85.3 98.2 100 100 100

13.4 22.1 31.8 45.6 63.7 83.5 100 100 44.0 56.2 67.3 79.1 95.4 100 100 100

51.2 65.9 79.3 93.7 100 100 100 100 58.6 77.3 94.1 100 100 100 100 100

31.9 42.8 55.7 68.3 89.5 100 100 100 50.8 64.5 76.2 92.3 100 100 100 100

30.4 42.0 53.7 65.3 78.5 98.4 100 100 39.6 54.7 70.3 91.2 100 100 100 100

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inhibitory concentration 50 (IC50) was calculated from Fig. 16 and Table 13. The results clearly revealed that most of the compounds possessed cytotoxic activity as evidenced by the IC50 values, as reported in Table 14. The results revealed that some tested compounds have

735

cytotoxic activity against the hepatocellular carcinoma (HePG-2) and mammary gland breast cancer (MCF-7) cell lines with superiority of HL3 (IC50 = 5.4 μg/mL and 5.6 μg/mL, respectively). All ligands HLn exhibit highly significant cytotoxic activity against HePG-2 cell line.

Fig. 16. Cytotoxic and antitumor activity of ligands (HLn) and their Co(II) complexes (1–5) against HePG-2 and MCF-7 cells.

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Fig. 16 (continued).

Among all the ligands tested against MCF-7 cell line HL3 is exhibiting very good cytotoxic activity, but ligands HL1, HL2, HL4 and HL5 are exhibiting good to moderate cytotoxic activity as shown in Table 14.

All cobalt(II) complexes are exhibiting moderate to weak cytotoxic or non-cytotoxic activity. Apparently, complexation reduces the cytotoxic activity of ligands. Comparing results with 5-fluorouracil (5-FU)

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739 Table 14 Inhibition of cell viability of ligands (HLn) and their Co(II) complexes (1–5) against HePG2 and MCF-7 cells in comparison with standard drug 5-fluorouracil. Compound 5-FU HL1 HL2 HL3 HL4 HL5 (1) (2) (3) (4) (5)

Cell lines [IC50 (μg/mL)] HePG-2

MCF-7

7.9 ± 0.24 8.3 ± 0.47 9.0 ± 0.68 5.4 ± 0.31 7.9 ± 0.38 10.3 ± 0.97 34.8 ± 3.15 12.4 ± 1.04 96.5 ± 6.35 37.1 ± 2.98 32.9 ± 2.32

5.6 ± 0.13 19.4 ± 1.27 41.5 ± 3.41 5.6 ± 0.21 17.6 ± 1.10 29.5 ± 1.29 81.6 ± 4.87 67.0 ± 4.11 N100 93.5 ± 6.37 62.7 ± 4.12

Data presented as mean ± SD. IC50 (μg/ml): 1–10 (very strong). 11–20 (strong). 21–50 (moderate). 51–100 (weak) and above 100 (non-cytotoxic). All the compounds and the standard dissolved in DMSO, diluted with culture medium containing 0.1% DMSO. The control cells were treated with culture medium containing 0.1% DMSO.

response indicated that HL3 have higher cytotoxic activity than 5-FU. The other compounds also showed cytotoxic activity but at higher IC50 values. The results indicated the importance of different heterocyclic rhodanine derivatives in enhancing the cytotoxic activity.

737

Table 16 Antibacterial and antifungal activities data of ligands (HLn) and their Co(II) complexes (1–5). Compound (mg/ml)

E. coli Diameter of inhibition zone (mm)

% activity index

S. aureus Diameter of inhibition zone (mm)

% activity index

Diameter of inhibition zone (mm)

C. albicans % activity index

HL1 HL2 HL3 HL4 HL5 (1) (2) (3) (4) (5) Ampicillin Colitrimazole

9 3 20 14 6 – – – – 3 24 –

37.5 12.5 83.3 58.3 25.0 – – – – 12.5 100 –

14 7 16 17 10 3 4 – 2 5 22 –

63.6 31.8 72.7 77.3 45.4 13.6 18.2 – 9.1 22.7 100 –

17 6 25 21 14 – – – – – – 26

65.4 23.1 96.1 80.8 53.8 – – – – – – 100

Co(II) complex of HL3 represented a lower antioxidant activity compared to its un-complexed compound. In accordance with the cytotoxicity testing results, the complexation decreases the biological activity of the synthesized compound.

3.12. Antioxidant activity 3.13. Antimicrobial activity Oxygen is vital for aerobic life process. However about 5% or more of the inhaled O2 is converted to reactive oxygen species (ROS). A free radical (FR) can be defined as a chemical species possessing an unpaired electron. FR can be positively charged, negatively charged or electrically neutral [48]. When generation of ROS overtakes the antioxidant defense of the cells, the free radicals start attacking the cell proteins, lipids and carbohydrates which leads to a number of physiological disorders [49]. Free radicals have been implicated in the pathogenesis of diabetes, liver damage, nephrotoxicity, inflammation, cancer, cardiovascular disorders, neurological disorders and in the process of aging [50]. Antioxidants are chemical substances that donate an electron to the free radical and convert it to a harmless molecule. They may reduce the energy of the free radical or suppress radical formation or break chain propagation or repair damage and reconstitute membranes. Table 15 expressed results of radical scavenging ability and percentage of inhibition of each ligands (HLn), their Co(II) complexes (1–5) and standard ascorbic acid, as a reference compound by ABTS method. The results showed that all ligands have high antioxidant activity and have asymptotic effect of ascorbic acid. HL3 presented the better activity among all other compounds and when compared with ascorbic acid. There are poor antioxidant activity for Co(II) complexes (1–5). The

Table 15 Results of radical scavenging activity and % of inhibition of each ligands (HLn) and their Co(II) complexes (1–5) by ABTS method. Compounds

Absorbance

% inhibition

Control of ABTS Ascorbic-acid HL1 HL2 HL3 HL4 HL5 (1) (2) (3) (4) (5)

0.520 0.057 0.070 0.082 0.055 0.068 0.079 0.332 0.296 0.424 0.339 0.283

0 89.0 86.5 84.2 89.4 86.9 84.8 36.1 43.1 18.5 34.8 45.6

The antimicrobial activity of ligands (HLn) and their Co(II) complexes (1–5) were tested against bacteria and fungi (yeast) for detecting their antimicrobial activities [9,51,52]. The used organisms in the present investigations included Gram negative (E. coli) bacteria, Gram positive (Staphylococcus aureus) and yeast (Candida albicans). The results of the antibacterial activities of the synthesized compounds are recorded in Table 16. All HLn were found to have antibacterial activity against Gram negative bacteria; namely; E. coli (inhibition zone =9 mm with activity index 37.5% for HL1, inhibition zone = 3 mm with activity index 12.5% for HL2, inhibition zone = 20 mm with activity index 83.3% for HL3, inhibition zone = 14 mm with activity index 58.3% for HL4 and inhibition zone = 6 mm with activity index 25% for HL5). Only complex (5) has antibacterial activity against Gram negative bacteria; namely; E. coli (inhibition zone = 3 mm with activity index 12.5%). All compounds under investigation have antibacterial activity against Gram positive bacteria; namely S. aureus (inhibition zone = 14 mm with activity index 63.6% for HL1, inhibition zone = 7 mm with activity index 31.8% for HL2, inhibition zone = 16 mm with activity index 72.7% for HL3, inhibition zone = 17 mm with activity index 77.3% for HL4, inhibition zone = 10 mm with activity index 45.4% for HL5, inhibition zone = 3 mm with activity index 13.6% for complex (1), inhibition zone = 4 mm with activity index 18.2% for complex (2), inhibition zone = 2 mm with activity index 9.1% for complex (4) and inhibition zone = 5 mm with activity index 22.7% for complex (5)) while complex (3) has no activity. Only ligands HLn have antifungal activity against C. albicans (inhibition zone = 17 mm with activity index 65.4% for HL1, inhibition zone = 6 mm with activity index 23.1% for HL2, inhibition zone = 25 mm with activity index 96.1% for HL3, inhibition zone = 21 mm with activity index 80.8% for HL4 and inhibition zone = 14 mm with activity index 53.8% for HL5). HLn were found to have high antibacterial and antifungal activities than their complexes (Fig. 17). HL3 was found to have high antibacterial activity against E. coli (Fig. 17a) and antifungal activity against C. albicans (Fig. 18) more than the other ligands. HL4 was found to have high antibacterial activity against S. aureus as shown in Fig. 17(b) more than other ligands. HL3 and HL4 are good antibacterial and antifungal agents.

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Fig. 17. Antibacterial activity data of ligands (HLn) and their Co(II) complexes against (a) Escherichia coli and (b) Staphylococcus aureus.

4. Conclusion The IR, 1H-NMR spectra show that ligands (HLn) exist in tautomeric between both states enol/hydrazo form with intramolecular hydrogen bonding. The ligands coordinate to cobalt(II) as monobasic tetradentate. The cobalt(II) complexes are non-electrolytes, paramagnetic and six-coordinated octahedral polymeric complexes of structure [(Co)2(Ln)2(HLn)(CH3COO)2(H2O)2]n. It is clear that, the four

bonding sites are 3-NH, CS, CO and hydrazo groups. The XRD patterns of ligands indicate that the powder is a mixture of amorphous and polycrystals nature. The polymeric complexes exhibit amorphous nature. The interaction between ligands (HLn) and SS-DNA involves a hypochromism effect coupled with bathochromism. There are straight line relationships between energy gap (ΔE) and the SS-DNA binding activity (Kb) of the ligands with Hammett's p-substitution coefficients (σR). It is clear that that the values of energy gap (ΔE) and the SS-

Fig. 18. Antifungal activity data of ligands (HLn) and their Co(II) complexes against Candida albicans.

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